Objective:To investigate the role of miRNA-4298/PADI4/p53 signal axis in mediating 4f-induced apoptosis of leukemia cells.Methods:The cell growth density was observed under inverted microscope and the proliferation of leukemia cells was detected by CCK-8 counting assay. The expression of PADI4 and P53 at mRNA level was detected by qRT-PCR. Cell cycle and apoptosis were measured with flow cytometry. The expression of PADI4, P53, Bcl-2, Bax, caspase-3 and caspase-9 at protein level was detected by Western blot. Differential miRNA and mRNA expression profiles was detected by next generation sequencing. Databases such as TargetScan were used to predict the potential upstream and downstream genes of PADI4. A luciferase reporter assay was used to detect the 3′UTR of PADI4 targeted by miRNA-4298. Cell transfection assay was used to detect the effect siRNA, PADI4 vector, miRNA mimics and miRNA inhibitor in interference and rescue.Results:Nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor 4f could inhibit the proliferation of THP-1, K562 and U937 cells, and induce the apoptosis of these leukemia cells. It downregulated the expression of PADI4 mainly through the binding activity of miRNA-4298 to miRNA sponges, which resulted in the proliferation inhibition and apoptosis of leukemia cells. The inhibited proliferation and apoptosis of leukemia cells by 4f were associated with the increase of P53 expression after the decrease of PADI4 expression. The PADI4-dependent upregulation of P53 led to the ratio inversion of downstream Bcl-2/Bax, which activated caspase-3 or caspase-9 to induce the apoptosis of leukemia cells.Conclusions:The apoptosis of leukemia cells induced by Nrf2 inhibitor 4f was mainly associated with the miRNA-4298/PADI4/p53 axis, suggesting that it might be a novel signaling pathway for targeted therapy.

A retrospective study was conducted on data of 23 patients with pancreatic duct diseases who were underwent peroral pancreatoscopy (POPS) at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from August 2020 to October 2022. The intraoperative observation, postoperative complications, and the diagnosis and treatment of POPS for pancreatic duct diseases were analyzed. All patients underwent POPS and achieved technical success. Among them, 7 patients were diagnosed as having intraductal papillary mucinous neoplasm of pancreas and 3 pancreatic malignant tumor. Eight patients with pancreatolithiasis accepted laser or eletrohydraulic lithotripsy under POPS. Abdominal pain improved in 2 patients with chronic pancreatitis after treatment. Melena disappeared in 2 patients with pancreatic duct hemorrhage or pancreatic enterostomy inflammation after conservative treatment. The symptom of 1 patient with pancreatic enterostomy stenosis improved after balloon dilation. There was no complication in the 23 patients, and the operation time was 35-90 min. The results indicate POPS is safe, effective with distinctive advantages in the diagnosis and treatment for pancreatic duct diseases.

Objective:To compare the population characteristics, the positive rate of screening, the detection rate of breast cancer, early diagnosis rate and the cost between the mass screening group and opportunistic screening group of breast cancer.Methods:This study is a prospective multicenter cohort study conducted from January 1, 2014 to December 31, 2016. The participants were enrolled for mass screening or opportunistic screening of breast cancer. After completing the questionnaire, all the participants received breast physical examination and breast ultrasound examination every year for 3 rounds by year. The participants′ characteristics and screening results of the two groups were compared by χ 2 test, Fisher exact test or Wilcoxon rank-sum test. Results:A total of 20 080 subjects were enrolled. In the mass screening group, 9 434 (100%), 8 111 (85.98%) and 3 940 (41.76%) cases completed the 3 rounds of screening, and 10 646 (100%), 6 209 (58.32%) and 2 988 (28.07%) cases in the opportunistic screening group, respectively. In the opportunistic screening group, the proportions of less than 3 months lactation (1 275/9 796 vs. 1 061/8 860, χ2=4.597, P=0.032), non-fertility (850/10 646 vs. 574/9 434, χ2=27.400, P<0.01), abortion history (6 384/10 646 vs. 5 062/9 434, χ2=81.232, P<0.01), postmenopausal (2 776/10 646 vs. 2 217/9 434, χ2=17.757, P<0.01), long-term oral contraceptives(>6 months) (171/10 646 vs. 77/9 434, χ2=25.593, P<0.01) and family history of breast cancer in first-degree relatives (464/10 646 vs. 236/9 434, χ2=51.257, P<0.01) were significantly higher than those in mass screening group. The positive rate of screening (514/10 646 vs. 128/9 434, χ2=194.736, P<0.01), the detection rate of breast cancer (158/10 646 vs. 13/9 434, χ2=107.374, P<0.01), and positive rate of biopsy (158/452 vs. 13/87, χ2=13.491, P<0.01) in the opportunistic screening group were significantly higher than those of the mass screening group. The early diagnosis rate of the mass screening group was significantly higher than the opportunistic screening group (10/12 vs. 66/141, χ2=5.902, P=0.015). The average cost for detecting each breast cancer case of the mass screening group was 215 038 CNY, which was 13.6 times of the opportunistic screening group (15 799 CNY/case). In the opportunistic screening group, the positive rate of biopsy in primary hospitals was significantly lower than that in large-volume hospitals (79/267 vs. 79/185, χ2=8.267, P=0.004), but there was no significant difference in the mass screening group (6/37 vs. 7/50, χ2=0.082, P=0.774). Conclusions:Breast cancer screening can improve early detection rate. Compared with the mass screening mode, the opportunistic screening mode has the advantages of higher proportion of high-risk factors, higher positive rate of screening, higher detection rate of breast cancer, higher positive rate of biopsy, and lower cost of screening. However, the early diagnosis rate of breast cancer of opportunistic screening is lower than that of mass screening. The positive rate of opportunistic screening in primary hospitals is lower than that of large-volume hospitals. The two screening modes have their own advantages and should be chosen according to local conditions of different regions in China.

Objective:To explore the epidemiological characteristics and treatment outcomes of patients with inhalation injuries combined with total burn area less than 30% total body surface area (TBSA).Methods:A retrospective observational study was performed on medical records of 266 patients with inhalation injuries combined with total burn area less than 30%TBSA who were admitted to the First Affiliated Hospital of Naval Medical University from January 2008 to December 2016 and met the inclusion criteria. The following statistical data of the patients were collected, including gender, age, injury site, injurious factors of inhalation injury, degree of inhalation injury, combined total burn area, tracheotomy, time of tracheotomy, mechanical ventilation, whether stayed in intensive care unit (ICU) or not, microbial culture results of bronchoalveolar lavage fluid, length of hospital stay, length of ICU stay, mechanical ventilation days, and respiratory tract infections. Single factor and multivariate linear regression analysis were used to screen out the risk factors impacting the length of hospital stay, length of ICU stay, and mechanical ventilation days of patients. Single factor and multivariate logistic regression analysis were used to screen out the risk factors impacting respiratory tract infections of patients.Results:The 266 patients included 190 males and 76 females, with the majority age of above or equal to 21 years and below 65 years (217 patients). The major injury site was confined space. The major factor causing inhalation injury was hot air. Mild and moderate inhalation injuries were more common in patients. The combined total burn area was 9.00% (3.25%, 18.00%) TBSA. In 111 patients who had tracheotomy, most of them received the procedures before being admitted to the First Affiliated Hospital of Naval Medical University. The length of hospital stay of patients was 27 (10, 55) days. The length of ICU stay of 160 patients who were hospitalized in ICU was 15.5 (6.0, 40.0) days. The mechanical ventilation days of 109 patients who were conducted with mechanical ventilation were 6.0 (1.3, 11.5) days. A total of 119 patients were diagnosed with respiratory tract infections, with 548 strains including 35 types of pathogens isolated, mainly Gram-negative bacteria. Single factor linear regression analysis showed that age, injurious factors of inhalation injury, combined total burn area, degree of inhalation injury (moderate and severe), tracheotomy, mechanical ventilation, and respiratory tract infections were the factors impacting the length of hospital stay of patients ( β=-0.198, -0.224, 0.021, 0.127, 0.164, -0.298, 0.357, 0.447, 95% confidence interval (CI)=-0.397--0.001, -0.395--0.053, 0.015-0.028, 0.009-0.263, 0.008-0.319, -0.419--0.176, 0.242-0.471, 0.340-0.555, P<0.1). Multivariate linear regression analysis showed that with mechanical ventilation and respiratory tract infections were the independent risk factors impacting the length of hospital stay of patients ( β=0.146, 0.383, 95% CI=0.022-0.271, 0.261-0.506, P<0.05 or P<0.01). Single factor linear regression analysis showed that injurious factors of inhalation injury, combined total burn area, degree of inhalation injury (moderate and severe), tracheotomy (no tracheotomy and prophylactic tracheotomy), mechanical ventilation, and respiratory tract infections were the factors impacting the length of ICU stay of patients ( β=0.225, 0.008, 0.237, 0.203, -0.408, -0.334, 0.309, 0.523, 95% CI=0.053-0.502, 0.006-0.010, -0.018-0.457, -0.022-0.428, -0.575--0.241, -0.687--0.018, 0.132-0.486, 0.369-0.678, P<0.1). Multivariate linear regression analysis showed that with respiratory tract infections was the independent risk factor impacting the length of ICU stay of patients ( β=0.440, 95% CI=0.278-0.601, P<0.01). Single factor linear regression analysis showed that injury site, injurious factors of inhalation injury (smoke and chemical gas), combined total burn area, degree of inhalation injury (moderate and severe), tracheotomy (no tracheotomy and prophylactic tracheotomy), and respiratory tract infections were the factors impacting mechanical ventilation days of patients ( β=-0.300, 0.545, 0.163, 0.005, 0.487, 0.799, -0.791, -0.736, 0.300, 95% CI=-0.565--0.034, 0.145-0.946, 0.051-1.188, 0.001-0.009, 0.127-0.847, 0.436-1.162, -1.075--0.508, -1.243--0.229, 0.005-0.605, P<0.1). Multivariate linear regression analysis showed that smoke inhalation, severe inhalation injury, and respiratory tract infections were the independent risk factors impacting mechanical ventilation days of patients ( β=0.210, 0.495, 0.263, 95% CI=0.138-0.560, 0.143-0.848, 0.007-0.519, P<0.05 or P<0.01). Single factor logistic regression analysis showed that age, injury site, combined total burn area (10%-19%TBSA and 20%-29%TBSA), degree of inhalation injury (moderate and severe), tracheotomy (prophylactic tracheotomy and no tracheotomy), and mechanical ventilation were the factors impacting respiratory tract infections of patients (odds ratio=1.079, 0.815, 1.400, 1.331, 1.803, 1.958, 0.990, 0.320, 3.094, 95% CI=0.840-1.362, 0.641-1.044, 1.122-1.526, 1.028-1.661, 1.344-2.405, 1.460-2.612, 0.744-1.320, 0.241-0.424, 2.331-4.090, P<0.1). Multivariate logistic regression analysis showed that with mechanical ventilation was the independent risk factor impacting respiratory tract infections of patients (odds ratio=4.300, 95% CI=2.152-8.624, P<0.01). Conclusions:The patients with inhalation injuries combined with total burn area less than 30%TBSA are mainly young and middle-aged males. Smoke inhalation, degree of inhalation injury, with mechanical ventilation and respiratory tract infections are the factors that affect the outcomes of patients with inhalation injuries combined with total burn area less than 30%TBSA. Additionally, prophylactic tracheotomy shows its potential value in reducing respiratory tract infections in patients with moderate or severe inhalation injuries.

Objective:To compare the population characteristics, the positive rate of screening, the detection rate of breast cancer, early diagnosis rate and the cost between the mass screening group and opportunistic screening group of breast cancer.Methods:This study is a prospective multicenter cohort study conducted from January 1, 2014 to December 31, 2016. The participants were enrolled for mass screening or opportunistic screening of breast cancer. After completing the questionnaire, all the participants received breast physical examination and breast ultrasound examination every year for 3 rounds by year. The participants′ characteristics and screening results of the two groups were compared by χ 2 test, Fisher exact test or Wilcoxon rank-sum test. Results:A total of 20 080 subjects were enrolled. In the mass screening group, 9 434 (100%), 8 111 (85.98%) and 3 940 (41.76%) cases completed the 3 rounds of screening, and 10 646 (100%), 6 209 (58.32%) and 2 988 (28.07%) cases in the opportunistic screening group, respectively. In the opportunistic screening group, the proportions of less than 3 months lactation (1 275/9 796 vs. 1 061/8 860, χ2=4.597, P=0.032), non-fertility (850/10 646 vs. 574/9 434, χ2=27.400, P<0.01), abortion history (6 384/10 646 vs. 5 062/9 434, χ2=81.232, P<0.01), postmenopausal (2 776/10 646 vs. 2 217/9 434, χ2=17.757, P<0.01), long-term oral contraceptives(>6 months) (171/10 646 vs. 77/9 434, χ2=25.593, P<0.01) and family history of breast cancer in first-degree relatives (464/10 646 vs. 236/9 434, χ2=51.257, P<0.01) were significantly higher than those in mass screening group. The positive rate of screening (514/10 646 vs. 128/9 434, χ2=194.736, P<0.01), the detection rate of breast cancer (158/10 646 vs. 13/9 434, χ2=107.374, P<0.01), and positive rate of biopsy (158/452 vs. 13/87, χ2=13.491, P<0.01) in the opportunistic screening group were significantly higher than those of the mass screening group. The early diagnosis rate of the mass screening group was significantly higher than the opportunistic screening group (10/12 vs. 66/141, χ2=5.902, P=0.015). The average cost for detecting each breast cancer case of the mass screening group was 215 038 CNY, which was 13.6 times of the opportunistic screening group (15 799 CNY/case). In the opportunistic screening group, the positive rate of biopsy in primary hospitals was significantly lower than that in large-volume hospitals (79/267 vs. 79/185, χ2=8.267, P=0.004), but there was no significant difference in the mass screening group (6/37 vs. 7/50, χ2=0.082, P=0.774). Conclusions:Breast cancer screening can improve early detection rate. Compared with the mass screening mode, the opportunistic screening mode has the advantages of higher proportion of high-risk factors, higher positive rate of screening, higher detection rate of breast cancer, higher positive rate of biopsy, and lower cost of screening. However, the early diagnosis rate of breast cancer of opportunistic screening is lower than that of mass screening. The positive rate of opportunistic screening in primary hospitals is lower than that of large-volume hospitals. The two screening modes have their own advantages and should be chosen according to local conditions of different regions in China.

Objective:To investigate the function of miR-5581-5p and its interaction with tripartite motif 22 (TRIM22) during the terminal differentiation of human acute promyelocytic leukemia (APL) cells into granulocytes.Methods:APL cells (NB4) were differentiated into granulocytes by all-trans retinoic acid (ATRA), using dimethylsulfoxide (DMSO) as the control. The expression of TRIM22 was detected by real-time fluorescent quantitative PCR (qRT-PCR) and Western blotting, and the expression of miR-5581-5p was detected by qRT-PCR during cell differentiation. miRNA expression was regulated by cell transfection with miR-5581-5p mimic and inhibitor, and negative control was set, and qRT-PCR was used to verify the regulatory effect. Luciferase binding assay was performed to detect the presence of targeted binding. Western blotting was used to detect the expression of TRIM22 after miRNA differential expression. Flow cytometry was used to detect the effects of the regulation of miR-5581-5p on the differentiation of NB4 cells induced by ATRA.Results:After ATRA induced NB4 cells to differentiate into granulocytes, the gene expression level of TRIM22 was significantly higher than that of the control group (24.56±2.80 vs. 1.02±0.13; t=8.392, P=0.001). The level of protein expression was also significantly higher than that of the control group (0.80±0.01 vs. 0.17±0.01; t=44.900, P<0.001). The expression level of miR-5581-5p in NB4 cells differentiation group was significantly lower than that in the control group (0.14±0.02 vs. 1.01±0.08; t=10.840, P<0.001). The results of the dual luciferase reporter gene showed that the luciferase activity of the co-transfected miR-5581-5p mimic and TRIM22 WT group was significantly lower than that of the co-transfected miR-5581-5p mimic and TRIM22 MUT group (0.73±0.02 vs. 0.98±0.03; t=7.534, P=0.002). Western blotting showed that after transfection with miR-5581-5p inhibitor, the expression of TRIM22 was significantly higher than that of the negative control (0.44±0.01 vs. 0.21±0.01; t=18.290, P<0.001). While after transfection with miR-5581-5p mimic, the expression of TRIM22 decreased significantly compared with the negative control (0.62±0.01 vs. 0.80±0.02; t=6.402, P=0.003). CD11b expression of miR-5581-5p mimic group after ATRA treatment was significantly lower than that of the control group (45.80±1.80 vs. 56.61±1.88; t=4.159, P=0.014). The expression of CD11b in miR-5581-5p inhibitor group was significantly higher than that in the control group (66.48±2.54 vs. 52.60±1.70; t=4.539, P=0.011). Conclusion:miRNA-5581-5p can bind to TRIM22 3′UTR and negatively regulate TRIM22 expression. The decrease of miR-5581-5p can increase the expression of TRIM22, then promote the differentiation of ATRA-induced NB4 cells into granulocytes.

Objective To evaluate the efficacy and safety of tip-flexible ureterorenoscope (tf-URS) with holmium laser for one-stage management of parapelvic cyst.Methods The clinical data of 26 patients treated with tf-URS incision and drainage using holmium laser from February 2016 to August 2018 were reviewed.The study were including 15 male and 11 female patients,ranging from 32 to 68 years old,with an average of 53.5 years old.There were 24 cases of unilateral single renal parapelvic cyst and 2 cases of bilateral single renal parapelvic cyst.There were 4 cases in 26 cases with unilateral single renal parapelvic cyst and contralateral single renal cyst,2 cases with unilateral single renal parapelvic cyst and ipsilateral kidney of stones.The diameter of parapelvic cyst was 3.4-5.6 cm,average 4.8 cm.All patients had undergone holmium laser endo-decortication of parapelvic cyst by tf-URS.With general anesthesia,tf-URS accessed pelvis retrogradely and decorticated parapelvic cyst with 200 μm Holium laser to drainage the cyst to pelvis.If the tf-URS was not placed successfully for the first time,Double-J tubes were retained for 1-2 weeks before treatment.The operative time,hospitalization time,blood loss,postoperative complications and clinical symptoms were collected and analyzed.Results The one-time access success rate of insertion of ff-URS was 88.5％ (23/26).All operations were successful without severe complications.The average time of operation was 17.2 min,ranging from 11 to 25 min.In 3-30 months follow-up,the cysts disappeared in 22 patients and reduced by more than one half in 1 patients.Flank pain relieved in 19 patients.Conclusions Holmium laser endo-decortication of parapelvic cyst by tf-URS could be a simple,minimally invasive,safe and effective method for parapelvic cyst,which is worthy of further promotion and application in clinical practice.

Objective: To investigate the effects of two different sorbents(Carbon perfusion apparatus and Resin perfusion apparatus)in Double plasma molecular absorb syetem for liver failure treatment. Methods: A total of 152 cases with liver failure who were admitted to The Sixth People's Hospital of Zhengzhou, from June 2016 to May 2018 were selected and divided into DPMARS Carbon group (77 cases) and Resin group (75 cases). The two groups were observed in terms of liver function, prothrombin activity(PTA),Plasma albumin ,tumor necrosis factor alpha and interleukin-6 were detected and compared between the two groups before and after treatment. Results: ①The clinical symptoms improved in different degree in two groups, the recovery rate of Carbon cans Carbon perfusion apparatus group and Resin group separately were89.6% (69/77)、90.7% (68/75)(χ² = 0.048, P = 0.975), there were no statistical differences. There were no statistical differences between the two groups in untoward reactions(χ² = 0.235, P = 0.995), ②Compared with before treatment, TBil(t = 3.735, 3.728; P = 0.000, 0.000)、ALT(t = 5.117, 5.203; P = 0.000, 0.000)、TNF-α (t = 3.158, 3.094; P = 0.000, 0.002)、IL-6(t = 3.647, 3.559; P = 0.002, 0.003)decreased and ALB (t = 2.300, 3.065; P = 0.024, 0.003) increased significantly after treatment in both groups, and there were statistical differences. There were no signifiant differences in the changes in ALB(t = 0.316, 0.209; P = 0.657, 0.720) and PTA(t = 0.810, 0.843; P = 0.429, 0.516). ③After treatment, there were no signifiant differences in the changes in TBil、ALT、ALB、PTA、TNF-α、IL-6(t = 0.377、0.904、-1.133、-1.552、0.841、0.401; P = 0.952、0.283、0.826、0.094、0.154、0.457). Conclusion Double plasma molecular absorb syetem is effective in treating liver failure. Carbon perfusion apparatus or Resin perfusion apparatus can be combined with Specific bilirubin adsorption column for DPMARS in clinical treatment,and their effects are similar.

Nano-antibodies (Nbs) were first discovered in the peripheral blood of alpacas. Compared with traditional antibodies, Nbs have the characteristics of small volume, good stability, strong tissue permeability, and easy production through microbial systems, etc. They are currently the smallest known functional antigen-specific binding fragments. Therefore, Nbs have been considered as valuable proteins in recent years and widely used in many fields, such as basic research, new drug development, disease treatment and so on. This article reviews the structural and biochemical properties of Nbs and the research progress on Nbs in the fields of tumor diagnosis and treatment, as well as their application prospect.